Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr Aiguader 88, 08003 Barcelona, Spain.
Dermatology Department, Hospital Universitari Germans Trias i Pujol, Institut d'investigació Germans Trias I Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
Int J Mol Sci. 2024 Feb 15;25(4):2319. doi: 10.3390/ijms25042319.
RNA-binding proteins are emerging as critical modulators of oncogenic cell transformation, malignancy and therapy resistance. We have previously found that the RNA-binding protein Cold Shock Domain containing protein E1 (CSDE1) promotes invasion and metastasis of melanoma, the deadliest form of skin cancer and also a highly heterogeneous disease in need of predictive biomarkers and druggable targets. Here, we design a monoclonal antibody useful for IHC in the clinical setting and use it to evaluate the prognosis potential of CSDE1 in an exploratory cohort of 149 whole tissue sections including benign nevi and primary tumors and metastasis from melanoma patients. Contrary to expectations for an oncoprotein, we observed a global decrease in CSDE1 levels with increasing malignancy. However, the CSDE1 cytoplasmic/nuclear ratio exhibited a positive correlation with adverse clinical features of primary tumors and emerged as a robust indicator of progression free survival in cutaneous melanoma, highlighting the potential of CSDE1 as a biomarker of prognosis. Our findings provide a novel feature for prognosis assessment and highlight the intricacies of RNA-binding protein dynamics in cancer progression.
RNA 结合蛋白正在成为致癌细胞转化、恶性肿瘤和治疗耐药性的关键调节因子。我们之前发现，RNA 结合蛋白冷休克结构域蛋白 E1（CSDE1）促进黑色素瘤的侵袭和转移，黑色素瘤是最致命的皮肤癌形式，也是一种高度异质性疾病，需要预测生物标志物和可用药靶。在这里，我们设计了一种在临床环境中用于 IHC 的单克隆抗体，并将其用于评估 CSDE1 在包括良性痣和原发性肿瘤以及黑色素瘤患者转移的 149 个全组织切片的探索性队列中的预后潜力。与作为癌蛋白的预期相反，我们观察到随着恶性程度的增加 CSDE1 水平整体下降。然而，CSDE1 细胞质/核比值与原发性肿瘤的不良临床特征呈正相关，并成为皮肤黑色素瘤无进展生存期的有力指标，突出了 CSDE1 作为预后标志物的潜力。我们的发现为预后评估提供了一个新特征，并强调了 RNA 结合蛋白在癌症进展中的复杂性。
